Relation Between The ATF3,SRD5A2 And Isolated Hypospadias

Hypospadias is a malformation characterized by the urethra opening on the underside of the penis. The reported incidence of hypospadias is approximately l/250~l/300 live male births, making hypospadias one of the most common congenital malformations in children. Some research has documented that the incidence of this anomaly has been increasing during the last three decades, and most hypospadias are sporadic, without inheritance or family recurrence. Evidence for genetic factors in hypospadias come from the observation of families with monogenic inheritance and the feature of hypospadias in several genetic syndromes. Moreover, environmental factors may also contribute to the pathogenesis of hypospadias. Taken together hypospadias is a complex disorder caused by the combined influence of genetic and environmental factors.Normal male sex differentiation relies on the effect of androgen. The conversion of testosterone (T) to dihydrotestosterone (DHT), required for the full masculinization of the external genitalia and prostate in the male foetus, is catalysed by the 5a-reductase-2 enzyme, which is encoded by the SRD5A2 gene located on the short arm of chromosome 2. Extensive mutation screening in hypospadias have revealed disease associated sequence alterations predominantly in the steroid 5-alpha reductase (SRD5A2) gene and more than 40 different mutations have been reported so far in the SRD5A2 gene, most are missense or nonsense mutations. Previous works were focus on familial hypospadias or other genetic syndromes, and the association of SRD5A2 mutations with isolated hypospadias was rarely studied.Activating transcription factor 3 (ATF3) is a member of the ATF/CREB...